Project Summary/Abstract Traumatic brain injury (TBI) is a silent epidemic, which recently has been labeled the signature injury of current combat operations, a population often exposed to stressful stimuli and emotional trauma. While TBI is typically known to impair learning and memory for neutral events, traumatic fear memories are enhanced after TBI, consistent with increased prevalence of comorbid TBI and post-traumatic stress disorder (PTSD). Mechanisms that underlie the complex TBI-PTSD comorbidity and associated emotional consequences are poorly understood. Although categorized separately from the emotional consequences of TBI, common physical symptoms including phonophobia, hyperacusis, and sensory sensitivity in other modalities may interact and influence emotional and stress responses. Given the highly conserved and redundant connectivity between auditory and limbic networks, and their vulnerability to TBI, alterations in sensory processing after diffuse TBI may result in otherwise neutral stimuli adopting aversive properties and impacting the encoding of traumatic memories. Our findings demonstrate that diffuse TBI causes dynamic changes in plasticity within amygdala neurocircuitry known to underlie stress, emotion, and fear learning processes and that TBI-induced changes within auditory fear circuitry correspond to robustly enhanced contextual fear when footshocks are paired with white noise auditory stimuli, but not low frequency pure tones. This proposal will test the hypothesis that auditory sensitivity following diffuse TBI underlies enhanced fear learning to white noise. We will first determine whether diffuse TBI heightens sensitivity in emotional-auditory networks in a series of convergent and novel anatomical, immunohistochemical, and behavioral approaches. Second, using novel viral mediated technology that allows direct manipulation of activity in specific target projections, we will causally determine the involvement of auditory-amygdala network function during white noise fear conditioning on the observed enhanced fear phenotype after TBI. Findings from these studies could uncover a novel interaction between common TBI sequelae that has not been considered previously. Translational research on the underlying contributing mechanisms of posttraumatic stress after TBI is a critical line of work in need of immediate investigation to determine targets for treatments and preventions for human patients in both military and civilian contexts.